Association between a polygenic lipodystrophy genetic risk score and diabetes risk in the high prevalence Maltese population.

Publisher: Springer Verlag Country of Publication: Germany NLM ID: 9200299 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-5233 (Electronic) Linking ISSN: 09405429 NLM ISO Abbreviation: Acta Diabetol Subsets: MEDLINE

Publication: Berlin : Springer Verlag
Original Publication: Berlin : Springer International, c1991-

Diabetes Mellitus, Type 2*/genetics ; Diabetes Mellitus, Type 2*/epidemiology ; Genetic Risk Score* ; Lipodystrophy*/genetics ; Lipodystrophy*/epidemiology; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Body Mass Index ; Cross-Sectional Studies ; Insulin Resistance/genetics ; Malta/epidemiology ; Obesity/genetics ; Obesity/complications ; Obesity/epidemiology ; Prevalence

Background: Type 2 diabetes (T2DM) is genetically heterogenous, driven by beta cell dysfunction and insulin resistance. Insulin resistance drives the development of cardiometabolic complications and is typically associated with obesity. A group of common variants at eleven loci are associated with insulin resistance and risk of both type 2 diabetes and coronary artery disease. These variants describe a polygenic correlate of lipodystrophy, with a high metabolic disease risk despite a low BMI.
Objectives: In this cross-sectional study, we sought to investigate the association of a polygenic risk score composed of eleven lipodystrophy variants with anthropometric, glycaemic and metabolic traits in an island population characterised by a high prevalence of both obesity and type 2 diabetes.
Methods: 814 unrelated adults (n = 477 controls and n = 337 T2DM cases) of Maltese-Caucasian ethnicity were genotyped and associations with phenotypes explored.
Results: A higher polygenic lipodystrophy risk score was correlated with lower adiposity indices (lower waist circumference and body mass index measurements) and higher HOMA-IR, atherogenic dyslipidaemia and visceral fat dysfunction as assessed by the visceral adiposity index in the DM group. In crude and covariate-adjusted models, individuals in the top quartile of polygenic risk had a higher T2DM risk relative to individuals in the first quartile of the risk score distribution.
Conclusion: This study consolidates the association between polygenic lipodystrophy risk alleles, metabolic syndrome parameters and T2DM risk particularly in normal-weight individuals. Our findings demonstrate that polygenic lipodystrophy risk alleles drive insulin resistance and diabetes risk independent of an increased BMI.
(© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

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Keywords: Genetics; Insulin resistance; Lean; Polygenic lipodystrophy; Type 2 diabetes

Date Created: 20240127 Date Completed: 20240427 Latest Revision: 20240731

20240801

10.1007/s00592-023-02230-9

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